Drug delivery systems bile salts

The new cyclosporine formulation (Sandimmun Neoral, Novartis Pharmaceuticals Corporation, East Hanover, NJ) is a self-microemulsifying drug delivery system, which consists of the drug in a lipophilic solvent (corn oil), hydrophilic cosolvent (propylene glycol) surfactant and an antioxidant [37]. Upon contact with GI fluids, Sandimmun Neoral readily forms a homogenous, monophasic microemulsion, which allows the absorption of the drug molecules. Unlike Sandimmun, the formation of this microemulsion is independent of bile salt activity, and indeed, studies have shown that the absorption of cyclosporine from the new formulation is much less dependent on bile flow [38] and is unaffected by food intake [39],... 

Since 1970, there have been numerous reports detailing the advantages of liposomes as drug-delivery systems. However, in general these systems have not been successful for oral delivery. Some of the reasons may be related to 1) their lack of stability in the GI tract and 2) their susceptibility to changes in pH, bile salts, and lipases. In addition, it has been shown that liposome systems are immunogenic. 

Rastogi et al." ° published a study on enhancing the pharmacological efficacy of protein-loaded PCL-PEG-based polymerosomes. Insulin was selected as the model protein and was complexed with sodium deoxycholate, a naturally occurring bile salt. The prepared surfoplexes were efficiently encapsulated in PCL- and PEG-based polymer vesicles. It was found that with this drug delivery system, the initial burst effect was greatly reduced, and the therapeutic effect of insulin was increased by 2 h. 

As mentioned above, the rectal route is very attractive for systemic delivery of peptide and protein drugs, but rectal administration of peptides often results in very low bioavailability due to not only poor membrane penetration characteristics (transport barrier) but also due to hydrolysis of peptides by digestive enzymes of the GI tract (enzymatic barrier). Of these two barriers, the latter is of greater importance for certain unstable small peptides, as these peptides, unless they have been degraded by various proteases, can be transported across the intestinal membrane. Therefore, the use of protease inhibitors is one of the most promising approaches to overcome the delivery problems of these peptides and proteins. Many compounds have been used as protease inhibitors for improving the stability of various peptides and proteins. These include aprotinin, trypsin inhibitors, bacitracin, puromycin, bestatin, and bile salts such as NaCC and are frequently used with absorption enhancers for improvement in rectal absorption. 

Micellar solutions and microemulsions are also used for parenteral delivery of hydrophobic drugs. They are usually stabilized by large amounts of hydrophilic surfactants, such as bile salts and polysorbates. Owing to their small size, micelles are less readily recognized by the immune system, resulting in prolonged circulation [36]. An example of micellar formulation is Taxol , in which the active antitumor agent paclitaxel is solubilized in micelles of polyoxyl castor oil. 

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